March 28, 2012Life SciencesOpen Access

The dual endothelin converting enzyme/neutral endopeptidase inhibitor SLV-306 (daglutril), inhibits systemic conversion of big endothelin-1 in humans

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Why the study?

Does SLV-306 (daglutril) reduce the systemic conversion of big ET-1 and increase plasma ANP levels in healthy male volunteers?

Population

13 healthy male volunteers

Comparison

SLV-306 administered orally at three increasing… vs Placebo

Design

RCT, randomised, double blinded

Follow-up

short-term (during and post 40-minute infusion)

Authors

ASAlison SeedUniversity of Liverpool RKRhoda E. KucSkolkovo Institute of Science and Technology JMJanet J. MaguireUniversity of Cambridge

Discussion

Member takes

Implication

Demonstrates dual NEP/ECE inhibition in healthy volunteers; extends mechanistic evidence and supports trials in cardiovascular disease.

Structured PICO

Does SLV-306 (daglutril) reduce the systemic conversion of big ET-1 and increase plasma ANP levels in healthy male volunteers?

Population

13 healthy male volunteers

Intervention

SLV-306 (daglutril) administered orally at three increasing doses (target concentrations of 75, 300, 1200 ng/ml of active metabolite KC-12615), followed by big ET-1 infusion at 8 and 12 pmol/kg/min (20 min each)

Comparator

Placebo

Outcome

Systemic conversion of big ET-1 to mature peptide (measured by ET-1, C-terminal fragment, and big ET-1 levels) and plasma atrial natriuretic peptide (ANP) levelssurrogate

SLV-306 effectively inhibits both neutral endopeptidase and endothelin converting enzyme in humans, augmenting ANP and inhibiting ET-1 production, which may offer therapeutic benefits in cardiovascular disease.

Cite This Study

Seed et al. (2012) studied this question.

synapsesocial.com/papers/6a7226caa528af2d65c453ca https://doi.org/10.1016/j.lfs.2012.03.022

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The dual endothelin converting enzyme/neutral endopeptidase inhibitor SLV-306 (daglutril), inhibits systemic conversion of big endothelin-1 in humans

Discussion

Member takes

Implication

Structured PICO

Cite This Study

The dual endothelin converting enzyme/neutral endopeptidase inhibitor SLV-306 (daglutril), inhibits systemic conversion of big endothelin-1 in humans

Discussion

Member takes

Implication

Structured PICO

Cite This Study

Also Consider

Also Consider